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  1. Stubbs B, Koyanagi A, Schuch FB, Firth J, Rosenbaum S, Veronese N, et al.
    Acta Psychiatr Scand, 2016 12;134(6):546-556.
    PMID: 27704532 DOI: 10.1111/acps.12654
    OBJECTIVE: Physical activity (PA) is good for health, yet several small-scale studies have suggested that depression is associated with low PA. A paucity of nationally representative studies investigating this relationship exists, particularly in low- and middle-income countries (LMICs). This study explored the global association of PA with depression and its mediating factors.
    METHOD: Participants from 36 LMICs from the World Health Survey were included. Multivariable logistic regression analyses were undertaken exploring the relationship between PA and depression.
    RESULTS: Across 178 867 people (mean ± SD age = 36.2 ± 13.5 years; 49.9% male), the prevalence of depression and the prevalence of low PA were 6.6% and 16.8% respectively. The prevalence of low PA was significantly higher among those with depression vs. no depression (26.0% vs. 15.8%, P < 0.0001). In the adjusted model, depression was associated with higher odds for low PA (OR = 1.42; 95% CI = 1.24-1.63). Mediation analyses demonstrated that low PA among people with depression was explained by mobility limitations (40.3%), pain and discomfort (35.8%), disruptions in sleep and energy (25.2%), cognition (19.4%) and vision (10.9%).
    CONCLUSION: Individuals with depression engage in lower levels of PA in LMICs. Future longitudinal research is warranted to better understand the relationships observed.
    Study name: World Health Survey (Malaysia is a study site)
  2. Perna J, Bellato A, Ganapathy PS, Solmi M, Zampieri A, Faraone SV, et al.
    Mol Psychiatry, 2023 Dec;28(12):5011-5023.
    PMID: 37495888 DOI: 10.1038/s41380-023-02143-7
    AIM: To conduct a systematic review and meta-analysis assessing whether vision and/or eye disorders are associated with Autism Spectrum Disorder (ASD).

    METHOD: Based on a pre-registered protocol (PROSPERO: CRD42022328485), we searched PubMed, Web of Knowledge/Science, Ovid Medline, Embase and APA PsycINFO up to 5th February 2022, with no language/type of document restrictions. We included observational studies 1) reporting at least one measure of vision in people of any age with a diagnosis of ASD based on DSM or ICD criteria, or ADOS; or 2) reporting the prevalence of ASD in people with and without vision disorders. Study quality was assessed with the Appraisal tool for Cross-Sectional Studies (AXIS). Random-effects meta-analyses were used for data synthesis.

    RESULTS: We included 49 studies in the narrative synthesis and 46 studies in the meta-analyses (15,629,159 individuals distributed across multiple different measures). We found meta-analytic evidence of increased prevalence of strabismus (OR = 4.72 [95% CI: 4.60, 4.85]) in people with versus those without ASD (non-significant heterogeneity: Q = 1.0545, p = 0.7881). We also found evidence of increased accommodation deficits (Hedge's g = 0.68 [CI: 0.28, 1.08]) (non-significant heterogeneity: Q = 6.9331, p = 0.0741), reduced peripheral vision (-0.82 [CI: -1.32, -0.33]) (non-significant heterogeneity: Q = 4.8075, p = 0.4398), reduced stereoacuity (0.73 [CI: -1.14, -0.31]) (non-significant heterogeneity: Q = 0.8974, p = 0.3435), increased color discrimination difficulties (0.69 [CI: 0.27,1.10]) (non-significant heterogeneity: Q = 9.9928, p = 0.1890), reduced contrast sensitivity (0.45 [CI: -0.60, -0.30]) (non-significant heterogeneity: Q = 9.9928, p = 0.1890) and increased retinal thickness (=0.29 [CI: 0.07, 0.51]) (non-significant heterogeneity: Q = 0.8113, p = 0.9918) in ASD.

    DISCUSSION: ASD is associated with some self-reported and objectively measured functional vision problems, and structural alterations of the eye, even though we observed several methodological limitations in the individual studies included in our meta-analyses. Further research should clarify the causal relationship, if any, between ASD and problems of vision during early life.

    PROSPERO REGISTRATION: CRD42022328485.

  3. Bellato A, Perna J, Ganapathy PS, Solmi M, Zampieri A, Cortese S, et al.
    Mol Psychiatry, 2023 Jan;28(1):410-422.
    PMID: 35931758 DOI: 10.1038/s41380-022-01699-0
    AIM: To conduct the first systematic review and meta-analysis assessing whether attention-deficit/hyperactivity disorder (ADHD) is associated with disorders of the eye, and/or altered measures of visual function.

    METHOD: Based on a pre-registered protocol (PROSPERO: CRD42021256352), we searched PubMed, Web of Knowledge/Science, Ovid Medline, Embase and APA PsycINFO up to 16th November 2021, with no language/type of document restrictions. We included observational studies reporting at least one measure of vision in people of any age meeting DSM/ICD criteria for ADHD and in people without ADHD; or the prevalence of ADHD in people with and without vision disorders. Study quality was assessed with the Appraisal tool for Cross-Sectional Studies (AXIS). Random effects meta-analyses were used for data synthesis.

    RESULTS: We included 42 studies in the narrative synthesis and 35 studies in the meta-analyses (3,250,905 participants). We found meta-analytic evidence of increased risk of astigmatism (OR = 1.79 [CI: 1.50, 2.14]), hyperopia and hypermetropia (OR = 1.79 [CI: 1.66, 1.94]), strabismus (OR = 1.93 [CI: 1.75, 2.12]), unspecified vision problems (OR = 1.94 [CI: 1.38, 2.73]) and reduced near point of convergence (OR = 5.02 [CI: 1.78, 14.11]); increased lag (Hedge's g = 0.63 [CI: 0.30, 0.96]) and variability (Hedge's g = 0.40 [CI: 0.17, 0.64]) of the accommodative response; and increased self-reported vision problems (Hedge's g = 0.63 [CI: 0.44, 0.82]) in people with ADHD compared to those without ADHD (with no significant heterogeneity). We also found meta-analytic evidence of no differences between people with and without ADHD on retinal nerve fiber layer thickness (Hedge's g = -0.19 [CI: -0.41, 0.02]) and refractive error (Hedge's g = 0.08 [CI: -0.26, 0.42]) (with no significant heterogeneity).

    DISCUSSION: ADHD is associated with some self-reported and objectively ascertained functional vision problems, but not with structural alterations of the eye. Further studies should clarify the causal relationship, if any, between ADHD and problems of vision.

    TRIAL REGISTRATION: PROSPERO registration: CRD42021256352.

  4. Stubbs B, Vancampfort D, Veronese N, Kahl KG, Mitchell AJ, Lin PY, et al.
    Psychol Med, 2017 Sep;47(12):2107-2117.
    PMID: 28374652 DOI: 10.1017/S0033291717000551
    BACKGROUND: Despite the known heightened risk and burden of various somatic diseases in people with depression, very little is known about physical health multimorbidity (i.e. two or more physical health co-morbidities) in individuals with depression. This study explored physical health multimorbidity in people with clinical depression, subsyndromal depression and brief depressive episode across 43 low- and middle-income countries (LMICs).
    METHOD: Cross-sectional, community-based data on 190 593 individuals from 43 LMICs recruited via the World Health Survey were analysed. Multivariable logistic regression analysis was done to assess the association between depression and physical multimorbidity.
    RESULTS: Overall, two, three and four or more physical health conditions were present in 7.4, 2.4 and 0.9% of non-depressive individuals compared with 17.7, 9.1 and 4.9% among people with any depressive episode, respectively. Compared with those with no depression, subsyndromal depression, brief depressive episode and depressive episode were significantly associated with 2.62, 2.14 and 3.44 times higher odds for multimorbidity, respectively. A significant positive association between multimorbidity and any depression was observed across 42 of the 43 countries, with particularly high odds ratios (ORs) in China (OR 8.84), Laos (OR 5.08), Ethiopia (OR 4.99), the Philippines (OR 4.81) and Malaysia (OR 4.58). The pooled OR for multimorbidity and depression estimated by meta-analysis across 43 countries was 3.26 (95% confident interval 2.98-3.57).
    CONCLUSIONS: Our large multinational study demonstrates that physical health multimorbidity is increased across the depression spectrum. Public health interventions are required to address this global health problem.
    Study name: World Health Survey (Malaysia is a study site)
  5. Parlatini V, Bellato A, Gabellone A, Margari L, Marzulli L, Matera E, et al.
    Expert Rev Mol Diagn, 2024 Apr;24(4):259-271.
    PMID: 38506617 DOI: 10.1080/14737159.2024.2333277
    INTRODUCTION: Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental conditions and is highly heterogeneous in terms of symptom profile, associated cognitive deficits, comorbidities, and outcomes. Heterogeneity may also affect the ability to recognize and diagnose this condition. The diagnosis of ADHD is primarily clinical but there are increasing research efforts aiming at identifying biomarkers that can aid the diagnosis.

    AREAS COVERED: We first discuss the definition of biomarkers and the necessary research steps from discovery to implementation. We then provide a broad overview of research studies on candidate diagnostic biomarkers in ADHD encompassing genetic/epigenetic, biochemical, neuroimaging, neurophysiological and neuropsychological techniques. Finally, we critically appraise current limitations in the field and suggest possible ways forward.

    EXPERT OPINION: Despite the large number of studies and variety of techniques used, no promising biomarkers have been identified so far. Clinical and biological heterogeneity as well as methodological limitations, including small sample size, lack of standardization, confounding factors, and poor replicability, have hampered progress in the field. Going forward, increased international collaborative efforts are warranted to support larger and more robustly designed studies, develop multimodal datasets to combine biomarkers and improve diagnostic accuracy, and ensure reproducibility and meaningful clinical translation.

  6. Cortese S, Solmi M, Michelini G, Bellato A, Blanner C, Canozzi A, et al.
    World Psychiatry, 2023 Feb;22(1):129-149.
    PMID: 36640395 DOI: 10.1002/wps.21037
    Neurodevelopmental disorders - including attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder, communication disorders, intellectual disability, motor disorders, specific learning disorders, and tic disorders - manifest themselves early in development. Valid, reliable and broadly usable biomarkers supporting a timely diagnosis of these disorders would be highly relevant from a clinical and public health standpoint. We conducted the first systematic review of studies on candidate diagnostic biomarkers for these disorders in children and adolescents. We searched Medline and Embase + Embase Classic with terms relating to biomarkers until April 6, 2022, and conducted additional targeted searches for genome-wide association studies (GWAS) and neuroimaging or neurophysiological studies carried out by international consortia. We considered a candidate biomarker as promising if it was reported in at least two independent studies providing evidence of sensitivity and specificity of at least 80%. After screening 10,625 references, we retained 780 studies (374 biochemical, 203 neuroimaging, 133 neurophysiological and 65 neuropsychological studies, and five GWAS), including a total of approximately 120,000 cases and 176,000 controls. While the majority of the studies focused simply on associations, we could not find any biomarker for which there was evidence - from two or more studies from independent research groups, with results going into the same direction - of specificity and sensitivity of at least 80%. Other important metrics to assess the validity of a candidate biomarker, such as positive predictive value and negative predictive value, were infrequently reported. Limitations of the currently available studies include mostly small sample size, heterogeneous approaches and candidate biomarker targets, undue focus on single instead of joint biomarker signatures, and incomplete accounting for potential confounding factors. Future multivariable and multi-level approaches may be best suited to find valid candidate biomarkers, which will then need to be validated in external, independent samples and then, importantly, tested in terms of feasibility and cost-effectiveness, before they can be implemented in daily clinical practice.
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